Cancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. One of the well-known mechanisms of chemotherapy resistance is the change in the mitochondrial death pathways which occur when cells are under stressful situations, such as chemotherapy. Mitophagy, or mitochondrial selective autophagy, is critical for cell quality control because it can efficiently break down, remove, and recycle defective or damaged mitochondria. As cancer cells use mitophagy to rapidly sweep away damaged mitochondria in order to mediate their own drug resistance, it influences the efficacy of tumor chemotherapy as well as the degree of drug resistance. Yet despite the importance of mitochondria and mitophagy in chemotherapy resistance, little is known about the precise mechanisms involved. As a consequence, identifying potential therapeutic targets by analyzing the signal pathways that govern mitophagy has become a vital research goal. In this paper, we review recent advances in mitochondrial research, mitophagy control mechanisms, and their implications for our understanding of chemotherapy resistance.

Epithelial-mesenchymal transition (EMT) is designated as one of the prime causes of chemoresistance in many cancers. In our previous study we established that cisplatin resistance in ovarian cancer (OC) is associated with EMT using sensitive OV90 cells and its resistant counterparts OV90CisR1 and OV90CisR2. In this study, we revealed through RNAseq analysis that ITGA1 can play essential part in EMT mediated cisplatin resistance in OC. We found large number of EMT related terms predominant in the top gene ontologies (GO). We also found Extracellular matrix (ECM) and actin cytoskeleton genes highly altered in the resistant cells. This was further confirmed by the protein-protein interaction (PPI) analysis where we identified that the core ECM components e.g., collagen, fibronectin, metalloproteases and integrins possessed most interactions. The pathway analysis revealed the Wnt signaling as the leading pathway. Since integrins have significant interaction with Wnt signaling, we focused our study on integrins among which, ITGA1, ITGA6, ITGA11 and ITGAV were primarily altered. We validated our results by western blotting and found that ITGA1 was highly expressed in resistant cells. Additionally, the high ABCA5 (efflux transporter) expression in resistant cells also supports the EMT proposition. The western blotting also revealed high β-catenin expression in resistant cells confirming the high Wnt signaling activity. Further, we induced xenograft tumors in nude mice. The histopathological analysis confirmed the aggressive nature of resistant tumors and showed the presence of necrotic core which could be implicated to EMT. Finally, the immunohistochemical staining confirmed the high protein expression in resistant tumor.

Athymic mice are widely used in preclinical research to study tumor growth, metastasis, and the efficacy of conventional and targeted therapies. However, these animals are profoundly deficient in thymus-derived conventional T cells while retaining B cells and substantial innate immune function, creating a selective blind spot for treatment effects that require adaptive immune amplification. In addition, many modern chemotherapeutic agents act beyond direct tumor-cell-intrinsic cytotoxicity, relying instead on immunogenic cell death (ICD), antigen presentation, and host immune amplification. An intact immune system is essential for the full therapeutic benefit of these chemotherapy drugs, as agents like anthracyclines and oxaliplatin trigger ICD to recruit and prime T lymphocytes, turning localized tumor damage into systemic, durable protection. Conversely, T-cell deficiency shifts chemotherapy-induced effects toward immunosuppression; in athymic models, the absence of cytotoxic T-cells leaves tumor-associated macrophages and myeloid-derived suppressor cells unchecked, creating an immunosuppressive microenvironment that directly contributes to underestimation of the therapeutic efficacy which is ultimately used in intact immunity. From our perspective, while athymic nude models remain valuable for direct tumor-cell responses and establishing primary human xenografts, but may underestimate endpoints requiring conventional T-cell priming, effector function, checkpoint interactions, systemic tumor control, or immunological memory. We recommend that preclinical study designs adopt a context-appropriate model strategy pairing athymic models with syngeneic or humanized mouse systems to accurately capture the full therapeutic potential of host-dependent anticancer therapies.

A schwannoma is a tumor that arises from the Schwann cells of the peripheral nerves. Primary pulmonary schwannomas are extremely rare, although they can occur anywhere in the body. Symptoms of endobronchial schwannoma vary depending upon the extent of bronchi blockage by the tumor. Schwannoma is a benign tumor. However, there is a risk of recurrence if a lesion that has developed extraluminal growth is incompletely resected. Here, a 76-year-old female patient presented with dyspnea and cough. An endobronchial tumor was identified originating from the left lower lobe bronchus and had collapsed the left lower lobe and grown to block most of the left main bronchus. Video-assisted thoracic surgery was performed to resect the left lower lobe. The tumor was diagnosed as an ancient schwannoma.